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Nasopharyngeal NeoplasmsPhase 2NCT02269943

Safety and Efficacy of CC-486 in Previously Treated Patients With Locally Advanced or Metastatic Nasopharyngeal Carcinoma

A Phase 2 study testing CC-486 in people with Nasopharyngeal Neoplasms, run by Celgene at 25 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate the safety and efficacy of CC-486 in previously treated patients with locally advanced or metastatic nasopharyngeal carcinoma having failed one to two previous regimens, including platinum-based chemotherapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Nasopharyngeal Neoplasms
What is being tested?
CC-486
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
25 sitesin 9 countries
Study dates
13 Feb 2015to 20 Apr 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age = or > 18 years Histological or cytological diagnosis of undifferentiated or poorly differentiated nasopharyngeal carcinoma that is locally advanced or metastatic.
  • Disease progression either clinically or radiographically after 1-2 previous regimens.
  • Patient has received a platinum containing regimen. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Radiographically-documented measureable disease.
  • Adequate organ and bone marrow functions.
  • Willingness to follow pregnancy precautions.

Who cannot join

  • History of, or current brain metastasis. Any other malignancy within 5 years prior to randomization with the exception of adequately treated in situ carcinoma of the cervix, uteri, or non-melanomatous skin cancer (all treatment of which should have been completed 6 months prior to enrollment), in situ squamous cell carcinoma of the breast, or incidental prostate cancer.
  • Previous treatment with azacitidine (any formulation), decitabine, any other hypomethylating agent.
  • History of gastrointestinal disorder or defect. Impaired ability to swallow oral medication. Persistent diarrhea or malabsorption.
  • Active cardiac disease and human immunodeficiency virus (HIV) infection
  • Active bleeding; pathological condition that carries a high risk of bleeding; risk of pseudoaneurysm of the internal carotid artery and carotid blowout syndrome.
  • Major surgery within 14 days prior to starting Investigational Product or has not recovered from major side effects.
Show all 11Show fewer
  • Another investigational therapy within 28 days or 5 half lives of randomization/enrollment, whichever is shorter.
  • Patient has not recovered from the acute toxic effects of prior anticancer therapy, radiation, or major surgery/significant trauma.
  • Radiotherapy < or = 4 weeks or limited field radiation for palliation < or = 2 weeks prior to starting with the investigational product.
  • Pregnancy/Breast feeding
  • Any condition that places the patient at unacceptable risk if he/she were to participate in the study or that confounds the ability to interpret data from the study.

Trial locations and contacts

25 sites in 9 countries.

25 sites in 9 countries

United States5 sites

  • Winship Cancer Institute of Emory University

    Atlanta, Georgia, 30322

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Levine Cancer Institute

    Charlotte, North Carolina, 28204

  • University of Chicago

    Chicago, Illinois, 60637

  • Columbia Comprehensive Cancer Care Clinic

    Jefferson City, Missouri, 65101

Other trials in United States

France3 sites

  • Institut Hospitalier Franco-Britannique

    Levallois-Perret, 92300

  • Institut Curie

    Paris, 75005

  • Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

Singapore3 sites

  • National Cancer Center

    Singapore, 169-610

  • Singapore Oncology Consultants

    Singapore, 258500

  • Johns Hopkins Singapore International Medical Centre

    Singapore, 308433

Other trials in Singapore

Spain3 sites

  • Instituto Catalan de Oncologia-Hospital Duran

    Barcelona, 08907

  • Hospital Universitario Madrid Sanchinarro

    Madrid, 28050

  • Hospital Universitario de Salamanca

    Salamanca, 37007

Other trials in Spain

Taiwan3 sites

  • Chang Gung Medical Foundation, Kaohsiung Memorial Hospital

    Niao-Sung Hsiang Kaohsiung County, 83301

  • China Medical University Hospital

    Taichung, 40447

  • Taichung Veterans General Hospital

    Taichung, 40705

Other trials in Taiwan

Tunisia3 sites

  • Hopital Abderrahman Mami de Pneumo-Phtisiologie de l'Ariana

    Aryanah, 2080

  • Institut Salah Azaiez

    Bab Saadoun, 1006

  • Hospital Habib Bourguiba

    Sfax, 3029

Other trials in Tunisia

Canada2 sites

  • McGill University

    Montreal, Quebec, H2W 1S6

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Greece2 sites

  • University General Hospital of Heraklion

    Heraklion, 71110

  • Thermi Clinic

    Thessaloniki, 56429

Other trials in Greece

Italy1 site

  • Istituto Nazionale Dei Tumori

    Milan, 20133

Other trials in Italy

About this study

Official title: A Phase 2, Multicenter, International, Single Arm Study To Assess The Safety And Efficacy Of Single Agent Cc-486 (Oral Azacitidine) In Previously Treated Subjects With Locally Advanced Or Metastatic Nasopharyngeal Carcinoma

The purpose of this study is to evaluate the safety and efficacy of CC-486 in previously treated patients with locally advanced or metastatic nasopharyngeal carcinoma having failed one to two previous regimens, including platinum-based chemotherapy. Participants will be enrolled according to a Simon two-stage design; if the predefined activity is met (>4 responses [complete response; partial response {CR/PR}] out of the first 17 evaluable participants based on independent radiological assessment), then the study will continue to enroll an additional 34 participants. If 4 or less responses out of 17 are observed, then the study enrollment will be stopped.

Being tested
CC-486
Keywords
Metastatic nasopharyngeal carcinoma, oral azacitidine, oral AZA, CC-486, metastatic, recurrent, nasopharyngeal carcinoma, nasal, solid tumors, locally advanced, rare head and neck cancer, nasopharynx, single chemotherapy agent, Epstein-Barr Virus (EBV) + nasopharyngeal carcinoma, EBV-DN, Celgene, Sponsor-study, oral chemotherapy, phase 2, oral Vidaza
Medical subject headings
Nasopharyngeal Neoplasms, Nasopharyngeal Carcinoma, Neoplasm Metastasis, Recurrence, Head and Neck Neoplasms, Epstein-Barr Virus Infections, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CC-486Drug

    Also called oral azacitidine

Study groups in NCT02269943
Study groupRoleWhat they receive
CC-486ExperimentalCC-486 will be administered orally every day on Days 1-14 of a 21 day cycle at a dose of 300 mg. The first 6 participants of Asian-Pacific ethnicity will receive a starting dose of 200 mg. If there are no safety concerns, the 300 mg dose will be administered to all subsequent participants of Asian-Pacific ethnicity.
Receives: Drug: CC-486

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants Who Achieved a Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) Based on an Independent Radiology Assessment (IRA)

    Overall response rate was defined as the combined incidence of Complete Response (CR) or Partial Response (PR), confirmed no less than 4 weeks after the criteria for response were first met, based on independent radiology assessment according to RECIST 1.1 criteria.

    Complete response was defined as the disappearance of all target lesions and non-target lesions; Partial response is at least a 30% decrease from baseline in the sum of diameters of target lesions with no progression of non-target lesions and no new lesions or disappearance of target lesions with persistence of one or more non-target lesions from baseline.

    Measured: Tumor response was assessed every (Q) 6 weeks for the first 3 evaluations then Q 9 weeks until disease progression as of the cut-off date of 08 August 2017; the median duration of treatment was 257 days for the 200 mg dose and 114.5 days for 300 mg dose

  2. Kaplan Meier Estimate of Progression-Free Survival (PFS) Based on an Independent Radiology Assessment According to RECIST 1.1 Criteria

    PFS was defined as the time from the date of start of the study treatment to the date of disease progression or death (any cause) on or prior to the data cut-off date for the statistical analysis, whichever occurred earlier, based on an independent radiology assessment of response using RECIST v1.1 criteria. Progressive disease was defined as at least a 20% increase in the sum of diameters of target or non-target lesions from nadir or appearance of a new lesion.

    Measured: From Day 1 of documented disease progression; up to data cut off date of 08 August 2017; median follow-up time for censored participants was 12.3 months

Secondary outcomes (10)

  1. Kaplan Meier Estimate of Overall Survival

    Overall survival was the time from the first dose of study drug to patient death from any cause. Participants who did not die were censored at the last known time the patient was alive date or the clinical data cutoff date, whichever was earlier.

    Measured: From Day 1 of study treatment to the first date of progressive disease or death; up to data cut-off date of 08 August 2017; overall median follow-up time for censored participants was 20.4 months

  2. Percentage of Participants With Stable Disease for ≥ 16 Weeks From the Date of the First Treatment, or CR or PR According to RECIST 1.1 Criteria and Based on an Independent Radiology Assessment

    Disease Control Rate (DCR) was defined as the percentage of participants with a CR, PR, confirmed ≥ 4 weeks after the criteria for response were first met, or stable disease for ≥ 16 weeks from the first treatment, based on independent radiology assessment using RECIST 1.1 criteria. A complete response was defined as the disappearance of all target lesions and non-target lesions; a partial response is at least a 30% decrease from baseline in the sum of diameters of target lesions with no progression of non-target lesions and no new lesions or disappearance of target lesions with persistence of one or more non-target lesions from baseline. Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for progressive disease

    Measured: Tumor response was assessed every 6 weeks for the first 3 evaluations then every 9 weeks until disease progression. As of the cut-off date of 08 August 2017 the median duration of treatment was 257 days for the 200 mg dose and 114.5 days for 300 mg dose

  3. Number of Participants With Treatment Emergent Adverse Events

    Treatment-emergent adverse events (TEAEs) were defined as any adverse event (AE) or serious adverse event (SAE) that occurred or worsened on or after the day of the first dose of the investigational product (IP) through 28 days after the last dose of IP. In addition, any SAE with an onset date more than 28 day after the last dose of IP that was assessed by the investigator as related to IP was considered a TEAE. The severity of AEs was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 and based on the following scale: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death.

    Measured: From date of first dose of study treatment to 28 days after last dose of study treatment; up to final data cut-off date of 08 August 2017; median treatment duration was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg

  4. Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration Of CC-486 (AUC-t)

    Area under the plasma concentration-time curve from Time 0 to the time of the last quantifiable concentration, calculated by linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing.

    Measured: Blood samples for oral azacitidine PK assessment were collected prior to each dose (pre-dose) and over the 8-hour period following each dose (0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose or similar schedule).

  5. Area Under the Plasma Concentration -Time Curve From 0 Extrapolated to Infinity (AUC-inf, AUC0-∞) Of CC-486

    Area under the plasma concentration-time curve from Time 0 extrapolated to infinity, calculated as [AUCt + Ct/ λz]. Ct is the last quantifiable concentration. No AUC extrapolation was performed with unreliable λz. If AUC %Extrap was ≥25%, AUC inf was not reported.

    Measured: Blood samples for oral azacitidine PK assessment were collected prior to each dose (pre-dose) and over the 8-hour period following each dose (0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose or similar schedule).

  6. Maximum Observed Concentration (Cmax) Of CC-486

    Maximum observed plasma concentration, obtained directly from the observed concentration versus time data.

    Measured: Blood samples for oral azacitidine PK assessment were collected prior to each dose (pre-dose) and over the 8-hour period following each dose (0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose or similar schedule).

  7. Time to Reach Maximum Concentration (Tmax) Of CC-486

    Time to Cmax, obtained directly from the observed concentration versus time data.

    Measured: Blood samples for oral azacitidine PK assessment were collected prior to each dose (pre-dose) and over the 8-hour period following each dose (0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose or similar schedule).

  8. Terminal Half-Life (t1/2) of CC-486

    Terminal phase half-life in plasma, calculated as [(ln 2)/λz]. t1/2 was only calculated when a reliable estimate for λz could be obtained.

    Measured: Blood samples for oral azacitidine PK assessment were collected prior to each dose (pre-dose) and over the 8-hour period following each dose (0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose or similar schedule).

  9. Apparent Total Clearance (CL/F) Of CC-486

    Apparent volume of distribution, calculated as [(CL/F)/λz].

    Measured: Blood samples for oral azacitidine PK assessment were collected prior to each dose (pre-dose) and over the 8-hour period following each dose (0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose or similar schedule).

  10. Apparent Volume of Distribution (Vz/F) Of CC-486

    Apparent volume of distribution, calculated as [(CL/F)/λz].

    Measured: Blood samples for oral azacitidine PK assessment were collected prior to each dose (pre-dose) and over the 8-hour period following each dose (0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose or similar schedule).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Oct 2014 (estimated)
  2. Study start13 Feb 2015
  3. Primary completion20 Apr 2017
  4. Study completion20 Apr 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02269943
Sponsor's protocol ID
CC-486-NPC-001
Other IDs
2014-001745-25, 2014
Status last verified
Nov 2018
First submitted
17 Oct 2014
Last updated
12 Dec 2018
Data monitoring committee
No
Expanded access
Available

Publications

  • Von Hoff DD, Rasco DW, Heath EI, Munster PN, Schellens JHM, Isambert N, Le Tourneau C, O'Neil B, Mathijssen RHJ, Lopez-Martin JA, Edenfield WJ, Martin M, LoRusso PM, Bray GL, DiMartino J, Nguyen A, Liu K, Laille E, Bendell JC. Phase I Study of CC-486 Alone and in Combination with Carboplatin or nab-Paclitaxel in Patients with Relapsed or Refractory Solid Tumors. Clin Cancer Res. 2018 Sep 1;24(17):4072-4080. doi: 10.1158/1078-0432.CCR-17-3716. Epub 2018 May 15.

    PubMed 29764853

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CC-486 in people with Nasopharyngeal Neoplasms, run by Celgene at 25 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States, France, Singapore, Spain, Taiwan and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Who Achieved a Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) Based on an Independent Radiology Assessment (IRA) (time frame: Tumor response was assessed every (Q) 6 weeks for the first 3 evaluations then Q 9 weeks until disease progression as of the cut-off date of 08 August 2017; the median duration of treatment was 257 days for the 200 mg dose and 114.5 days for 300 mg dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02269943, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2018.

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